Construction and effects of functionalized graphene oxide nonparticles-mediated RNA interference of hypoxia-inducible factor-1α gene / 中华核医学与分子影像杂志

ABSTRACT

Objective To explore the effects of graphene oxide (GO)-polyethylene glycol (PEG)-folic acid (FA)-pyrenemethylamine hydrochloride (PyNH2)-mediated RNA interference (RNAi) of hypoxia-inducible factor-1α (HIF-1α) on the biological behaviors of human pancreatic cancer Patu8988 cells.Methods GO-PEG-FA-PyNH2 and RNAi targeting HIF-1α gene (GO-PEG-FA-PyNH2-HIF-1α-RNAi)was constructed.The expressions of HIF-1α and glucose transporter 1 (Glut-l) in Patu8988 cells were determined after knockdown of HIF-1α by RNAi.The invasive ability,the proliferation and the cell cycle of Patu8988 cells were investigated.The effect of HIF-1α knockdown on the uptake of 18F-fluorodeoxyglucose (FDG) in Patu8988 cells was also detected.Comparison of data was conducted by one-way analysis of variance and least significant difference t test.Results The GO-PEG-FA-PyNH2 was successfully constructed,and no cytotoxicity was found.Under the hypoxia or normoxia state,the mRNA and protein levels of HIF-1α and mRNA level of Glut-1 in cells transfected with GO-PEG-FA-PyNH2-HIF-1α-RNAi (study group) were lower than those in cells transfected with GO-PEG-FA-PyNH2 (negative group) and cells transfected with Opti-minimal essential medium (Opti-MEM,control group;F=30.25-32.58,t=3.66-5.81,all P＜0.05);the numbers of migrated cells in the study group were much lower than those in the negative group and the control group (F=38.63 and 41.35,t=20.51-35.25,all P＜0.01);the cell proliferation in the study group was significantly lower than that in the negative group and the control group (F=35.19 and 38.11,t =15.11-22.19,all P＜0.05).The proportions of G0/G1 cells in the study group were higher than those in the negative group and the control group (F=34.60 and 34.83,t=11.55-34.56,all P＜0.05);the 18 F-FDG uptake in the study group was lower than that in the negative group and control group (F=29.85 and 31.69,t =3.35-4.35,all P＜0.05).Conclusion GO-PEG-FA-PyNH2-mediated HIF-1α RNAi inhibits the expression of HIF-1α in pancreatic cancer cells,leading to changes in related biological behaviors.